Anemia

Signs and symptoms

Anemia goes undetected in many people, and symptoms can be small and vague. Most commonly, people with anemia report a feeling of weakness or fatigue in general or during exercise, general malaise and sometimes poor concentration. People with more severe anemia often report dyspnea (shortness of breath) on exertion. Very severe anemia prompts the body to compensate by increasing cardiac output, leading to palpitations and sweatiness, and to heart failure. Pallor (pale skin, mucosal linings and nail beds) is often a useful diagnostic sign in moderate or severe anemia, but it is not always apparent. Other useful signs are cheilosis(angular stomatitis)and koilonychias( Spoon nails). Pica, the consumption of non-food based items such as dirt, paper, wax, grass, ice, and hair, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of hemoglobin. Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced scholastic performance in children of school age.

Diagnosis

Generally, clinicians request complete blood counts in the first batch of blood tests in the diagnosis of an anemia. Apart from reporting the number of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anemia.. In modern counters, four parameters (RBC count, hemoglobin concentration, MCV and RDW, red blood cell distribution width) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated, and compared to values adjusted for age and sex. Some counters estimate hematocrit from direct measurements. For adult men, a hemoglobin level less than 13.0 g/dl is diagnostic of anemia, and for adult women, the diagnostic threshold is below 12.0 g/dl.

Classification

Production vs. destruction or loss

This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyte (precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction and/or loss. Clinical signs of loss or destruction include abnormal peripheral blood smear with signs of hemolysis; elevated LDH suggesting cell destruction; or clinical signs of bleeding, such as guiaic-positive stool, radiographic findings, or frank bleeding.

The following is a simplified schematic of this approach:

Anemia
Reticulocyte production index shows inadequate production response to anemia. / Reticulocyte production index shows appropriate response to anemia = ongoing hemolysis or blood loss without RBC production problem.
No clinical findings consistent with hemolysis or blood loss: pure disorder of production. / Clinical findings and abnormal MCV: hemolysis or loss and chronic disorder of production*. / Clinical findings and normal MCV= acute hemolysis or loss without adequate time for bone marrow production to compensate**.
Macrocytic anemia (MCV>100) / Normocytic anemia (80<MCV<100) / Microcytic anemia (MCV<80)

Red blood cell size

In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volume (MCV). If the cells are smaller than normal (under 80 fl), the anemia is said to be microcytic; if they are normal size (80-100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as macrocytic. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of iron deficiency. Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cells may point to a cause in the bone marrow.

Microcytic anemia

Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:

·  Heme synthesis defect

o  Iron deficiency anemia

o  Anemia of chronic disease (more commonly presenting as normocytic anemia)

·  Globin synthesis defect

o  alpha-, and beta-thalassemia

o  HbE syndrome

o  HbC syndrome

o  and various other unstable hemoglobin diseases

·  Sideroblastic defect

o  Hereditary sideroblastic anemia

o  Acquired sideroblastic anemia, including lead toxicity

o  Reversible sideroblastic anemia

Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.

·  Iron deficiency anemia is caused by insufficient dietary intake or absorption of iron to replace losses from menstruation or losses due to diseases. Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red blood cells. In the United States, 20% of all women of childbearing age have iron deficiency anemia, compared with only 2% of adult men. The principal cause of iron deficiency anemia in premenopausal women is blood lost during menses. Studies have shown that iron deficiency without anemia causes poor school performance and lower IQ in teenage girls. Iron deficiency is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips (angular stomatitis).

·  Iron deficiency anemia can also be due to bleeding lesions of the gastrointestinal tract. Fecal blood testing, upper endoscopy and lower endoscopy should be performed to identify bleeding lesions. In men and post-menopausal women the chances are higher that bleeding from the gastrointestinal tract could be due to colon polyp or colorectal cancer.

·  Worldwide, the most common cause of iron deficiency anemia is parasitic infestation (hookworm, amebiasis, schistosomiasis and whipworm).

Macrocytic anemia

·  Megaloblastic anemia, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid (or both). Deficiency in folate and/or vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does.

o  Pernicious anemia is caused by a lack of intrinsic factor. Intrinsic factor is required to absorb vitamin B12 from food. A lack of intrinsic factor may arise from an autoimmune condition targeting the parietal cells (atrophic gastritis) that produce intrinsic factor or against intrinsic factor itself. These lead to poor absorption of vitamin B12.

o  Macrocytic anemia can also be caused by removal of the functional portion of the stomach, such as during gastric bypass surgery, leading to reduced vit B12/folate absorption. Therefore one must always be aware of anemia following this procedure.

·  Hypothyroidism

·  Alcoholism commonly causes a macrocytosis, although not specifically anemia. Other types of Liver Disease can also cause macrocytosis.

·  Methotrexate, zidovudine, and other drugs that inhibit DNA replication.

Macrocytic anemia can be further divided into "megaloblastic anemia" or "non-megaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which result in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (6-10 lobes). The non-megaloblastic macrocytic anemias have different etiologies (i.e. there is unimpaired DNA globin synthesis,) which occur, for example in alcoholism.

Normocytic anemia

Normocytic anaemia occurs when the overall hemoglobin levels are always decreased, but the red blood cell size (Mean corpuscular volume) remains normal. Causes include:

·  Acute blood loss

·  Anemia of chronic disease

·  Aplastic anemia (bone marrow failure)

·  Hemolytic anemia

Dimorphic anemia

When two causes of anemia act simultaneously, e.g., macrocytic hypochromic, due to hookworm infestation leading to deficiency of both iron and vitamin B12 or folic acid or following a blood transfusion more than one abnormality of red cell indices may be seen. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), which suggests a wider-than-normal range of red cell sizes.

Heinz body anemia

Heinz bodies form in the cytoplasm of RBCs and appear like small dark dots under the microscope. There are many causes of Heinz body anaemia, and some forms can be drug induced. It is triggered in cats by eating onions or acetaminophen .

Specific anemias

·  Anemia of prematurity occurs in premature infants at 2 to 6 weeks of age and results from diminished erythropoietin response to declining hematocrit levels.

·  Aplastic anemia is a condition generally unresponsive to anti-anemia therapies where bone marrow fails to produce enough red blood cells.

·  Fanconi anemia is an hereditary disorder or defect featuring aplastic anemia and various other abnormalities.

·  Hemolytic anemia causes a separate constellation of symptoms (also featuring jaundice and elevated LDH levels) with numerous potential causes. It can be autoimmune, immune, hereditary or mechanical (e.g. heart surgery). It can result (because of cell fragmentation) in a microcytic anemia, a normochromic anemia, or (because of premature release of immature red blood cells from the bone marrow), a macrocytic anemia.

·  Hereditary spherocytosis is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen. This leads to a decrease in the number of circulating RBCs and, hence, anemia.

·  Sickle-cell anemia, a hereditary disorder, is due to homozygous hemoglobin S genes.

·  Warm autoimmune hemolytic anemia is an anemia caused by autoimmune attack against red blood cells, primarily by IgG.

·  Cold agglutinin hemolytic anemia is primarily mediated by IgM.

Possible complications

Anemia diminishes the capability of individuals who are affected to perform physical activities. This is a result of one's muscles being forced to depend on anaerobic metabolism. The lack of iron associated with anemia can cause many complications, including hypoxemia, brittle or rigid fingernails, cold intolerance, and possible behavioral disturbances in children. Hypoxemia resulting from anemia can worsen the cardio-pulmonary status of patients with pre-existing chronic pulmonary disease. Cold intolerance occurs in one in five patients with iron deficiency anemia .

Anemia during pregnancy

During pregnancy, women should be especially aware of the symptoms of anemia, as an adult female loses an average of two milligrams of iron daily. Therefore, she must intake a similar quantity of iron in order to make up for this loss. Additionally, a woman loses approximately 500 milligrams of iron with each pregnancy, compared to a loss of 4-100 milligrams of iron with each period. Possible consequences for the mother include cardiovascular symptoms, reduced physical and mental performance, reduced immune function, fatigue, reduced peripartal blood reserves and increased need for blood transfusion in the postpartum period.

5